In human senile nuclear cataracts the lens crystallins undergo oxidative damage which leads to the formation of proteins that are pigmented, develop a characteristic non-tryptophan fluorescence and are cross-linked by non-disulfide covalent bonds. It has been believed that photo-oxidation of aromatic amino acid residues may be responsible for these changes. We have now demonstrated what we believe to be a more attractive mechanism for formation of these altered lens crystallins, i.e. photosensitized oxidation mediated by singlet oxygen. We have shown that such a system which involves light, a photosensitizing molecule and oxygen can mimic these changes in vitro since solutions of lens crystallins exposed to such a system undergo each of the modifications outlined above. In addition crystallins in intact lenses irradiated in the presence of photosensitizers are also susceptible to these changes. In contrast to the direct photo-oxidation of aromatic residues this system is dependent upon near UV light of wavelengths which readily penetrate to the lens. Since we have been able to demonstrate the presence of effective near UV absorbing photosensitizers in human lens we believe that this mechanism may be a major factor in the etiology of human senile cataract.